Project description:While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many. Existing non-hormonal contraceptives include permanent sterilization, copper intrauterine devices (IUDs), chemical/physical barriers such as spermicides and condoms, as well as traditional family planning methods including withdrawal and the rhythm method. Individuals who wish to retain their fertility in the future can achieve highest adherence and efficacy with long-acting, reversible contraceptives (LARCs), though there is only one, the copper IUD, that is non-hormonal. As rates of unintended pregnancies remain high with existing contraceptive options, it is becoming increasingly attractive to develop novel pregnancy prevention methods for both women and men. Non-hormonal contraceptives can target a variety of critical reproductive processes discussed here. This review focuses on identified non-hormonal contraceptive targets and subsequent drug candidates in development.
Project description:Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.
Project description:OBJECTIVE:To assess strategies to improve safe-sex practices in sexually active female adolescents living with HIV, through linking reproductive health (RH) care with HIV care. METHODS:A single arm, 48-week prospective study was conducted with 77 sexually active adolescents in five sites in Thailand. Guided RH education was carried out through video, brochures and individual counselling. Participants were offered free effective contraception (EC), in addition to a barrier method (dual contraception) versus barrier method only. Changes in EC use were assessed with McNemar's test; predicting factors with logistic regression. RESULTS:Median age was 19 years; 95% were perinatally infected; 30% had been pregnant. All but one showed RH-knowledge improvement after RH education. Individual counselling was most often rated the 'most helpful' educational method. At the screening visit 21% were using dual contraception; 53% a male condom only; 8% EC method only; and 18% were not using any contraceptive method. Dual-contraception use improved with time, reaching 74% at week 48. EC-use at the baseline visit was associated with having ever used EC prior to study entry (P<0.0001), and the study site (P<0.0001). Having ever used EC was associated with a history of pregnancy (P=0.0085) and forced sex (P=0.0386). CONCLUSION:Offering continuous RH care, linked with HIV care, resulted in increased use of dual contraception. Healthcare providers played a significant role in the process. RH education should address the main predictors for EC use by adolescents, including past, personal experience.
Project description:ObjectiveWe sought to compare complication and continuation rates of the levonorgestrel intrauterine system (LNG-IUS) with the subdermal etonogestrel (ENG) implant across the United States among girls and women 15-44 years of age.Study designA retrospective study of health insurance claims records from 2007 through 2011 identified a cohort of women who had LNG-IUS (n = 79,920) or ENG implants (n = 7374) inserted and had insurance coverage for 12 months postinsertion. Claims for complications were examined 12 months after insertion, or until removal of either device within each of 3 age groups.ResultsAfter its introduction in 2007, the frequency of ENG implants increased each year and almost a third of all insertions were in teenagers. However, among women ≤24 years old who had delivered an infant in the prior 8 weeks, a LNG-IUS was more likely to be inserted than an ENG implant (P < .05). The most frequent complications with both methods were related to abnormal menstruation, which was more likely to occur among ENG implant users. Overall, 83-88% of the entire sample used their chosen method for at least 12 months. The odds of continuation were similar for both methods among teenagers, but ENG implants were more likely to be removed prematurely among women 20-24 years old (odds ratio, 1.21; 95% confidence interval, 1.06-1.39) and 25-44 years old (odds ratio, 1.49; 95% confidence interval, 1.35-1.64).ConclusionBoth of these long-acting contraceptive methods are well tolerated among women of all ages, and demonstrate high continuation rates.
Project description:Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.
Project description:Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition. Also, young (18-24 years) but not older women who used DMPA and COCs were at increased HIV risk.
Project description:ObjectivesNew Mexico is a large rural state with high rates of unintended pregnancy and limited access to contraception. In 2017, the New Mexico Pharmacist Prescriptive Authority Act was amended to allow pharmacists to prescribe hormonal contraception. We explored pharmacist perspectives on prescribing hormonal contraceptives, including perceived barriers and facilitators to implementation in rural New Mexico and opinions on over-the-counter (OTC) access, and prescribing and inserting subdermal contraceptive implants.MethodsThis qualitative study recruited rural pharmacists using contact information from the New Mexico Board of Pharmacy and at a state-level pharmacist conference. We conducted semistructured telephone interviews with pharmacists focusing on benefits and concerns about prescribing hormonal contraception, resources required, perspectives on OTC access, and interest in prescribing and placing contraceptive implants. Deidentified transcribed interviews were analyzed by 2 independent coders for emerging themes.ResultsFrom November 2017 to January 2018, we recruited 25 rural pharmacists and conducted 21 interviews. The majority of participants were male (71%), aged over 60 years (43%), and in practice for over 20 years (52%). Interviewees were mostly positive about prescribing hormonal contraception citing community benefits. The top 3 perceived barriers were training needs, reimbursement, and liability. The top 3 facilitators were the availability of private areas within pharmacies, pharmacists' role as knowledgeable health care team members, and pharmacist accessibility without appointments. Most pharmacists did not support OTC access to hormonal contraception, and over half were interested in certification to prescribe and place subdermal contraceptive implants.ConclusionNew Mexico pharmacists identified community benefits of pharmacy access to hormonal contraception and were interested in training. Several barriers must be addressed to realize the potential of this practice expansion.
Project description:To compare etonogestrel pharmacokinetic and pharmacodynamic outcomes by both self-reported race/ethnicity and genetically determined ancestry among contraceptive implant users. We conducted a secondary analysis of our parent pharmacogenomic study of 350 implant users. We genotyped these reproductive-aged (18-45 years) women for 88 ancestry-informative single nucleotide polymorphisms. We then assigned each participant a proportion value for African (AFR), European (EUR), and Indigenous American (AMR) ancestry based on reference population data. We correlated genetic ancestry with self-reported race/ethnicity and utilized genetic ancestry proportion values as variables for previously performed association analyses with serum etonogestrel concentrations and progestin-related side effects (e.g., bothersome bleeding and subjective weight gain). We successfully estimated genetically determined ancestry for 332 participants. EUR, AFR, and AMR ancestry were each highly correlated with self-reported White/non-Hispanic race (r = 0.64, p = 4.14 × 10-40 ), Black/African American race (r = 0.88, p = 1.36 × 10-107 ), and Hispanic/Latina ethnicity (r = 0.68, p = 4.03 × 10-47 ), respectively. Neither genetically determined ancestry nor self-reported race/ethnicity were significantly associated with serum etonogestrel concentrations. AFR ancestry and self-reported Black race had similar associations with reporting monthly periods (odds ratio [OR] 2.18, p = 0.09 vs. OR 2.22, p = 0.02) and having received treatment for bothersome bleeding (OR 5.19, p = 0.005 vs. OR 4.73, p = 2.0 × 10-4 ). In multivariable logistic regression for subjective weight gain, AMR ancestry dropped out of the model in preference for self-reported Hispanic/Latina ethnicity. We found no new associations between genetically determined ancestry and contraceptive implant pharmacodynamics/pharmacokinetics. Self-reported race/ethnicity were strong surrogates for genetically determined ancestry among this population of contraceptive implant users. Our data suggest that self-reported race/ethnicity, capturing societal and cultural aspects, remain important to the investigation of progestin-related side effects.
Project description:Importance:Since 2016, 11 states have expanded the scope of pharmacists to include direct prescription of hormonal contraception. Dispensing greater than 1 month's supply is associated with improved contraceptive continuation rates and fewer breaks in coverage. Scant data exist on the practice of pharmacist prescription of contraception and its outcomes compared with traditional, clinic-based prescriptions. Objective:To compare the amount of hormonal contraceptive supply dispensed between pharmacists and clinic-based prescriptions. Prescribing patterns were assessed by describing prescribing practices for women with contraindications to combined hormonal contraception. Characteristics of women seeking hormonal contraception directly from pharmacists were also described. Design, Setting, and Participants:This cohort study surveyed women aged 18 to 50 years who presented to pharmacies in California, Colorado, Hawaii, and Oregon for hormonal contraception prescribed by a clinician or a pharmacist between January 30 and November 1, 2019. Exposures:Pharmacist or clinic-based prescription of contraception. Main Outcomes and Measures:Months of contraceptive supply dispensed. Results:Four hundred ten women (mean [SD] age, 27.1 [7.7] years) were recruited who obtained contraception directly from a pharmacist (n = 144) or by traditional clinician prescription (n = 266). Women obtaining contraception from a pharmacist were significantly younger (82 [56.9%] vs 115 [43.2%] participants aged 18-24 years; P = .03), had less education (38 [26.4%] vs 100 [37.6%] with a bachelor degree; P = .002), and were more likely to be uninsured (16 [11.1%] vs 8 [3.0%] participants; P = .001) compared with women with a prescription from a clinician. Pharmacists were significantly more likely to prescribe a 6-month or greater supply of contraceptives than clinicians (6.9% vs 1.5%, P < .001) and significantly less likely to only prescribe a 1-month supply (42 [29.2%] vs 118 [44.4%] prescriptions; P < .001). Controlling for all covariates, women seen by pharmacists had higher odds of receipt of a 6-month or greater supply of contraceptives compared with those seen by clinicians (odds ratio = 3.55; 95% CI, 1.88-6.70). Pharmacists were as likely as clinicians to prescribe a progestin-only method to women with a potential contraindication to estrogen (n = 60 women; 8 [20.0%] vs 6 [30.0%], P = .52). Conclusions and Relevance:These findings suggest that pharmacist prescription of contraception may be associated with improved contraceptive continuation by preventing breaks in coverage through the provision of a greater supply of medication. Efforts are needed to educate prescribing providers on the importance of dispensing 6 months or greater contraceptive supply.
Project description:BackgroundAdherence to antiplatelet medications is critical to prevent life threatening complications (ie, stent thrombosis) after percutaneous coronary interventions (PCIs), yet rates of nonadherence range from 21-57% by 12 months. Mobile interventions delivered via text messaging or mobile apps represent a practical and inexpensive strategy to promote behavior change and enhance medication adherence.ObjectiveThe Mobile4Meds study seeks to determine whether text messaging or a mobile app, compared with an educational website control provided to all Veterans, can improve adherence to antiplatelet therapy among patients following acute coronary syndrome (ACS) or PCI. The three aims of the study are to: (1) determine preferences for content and frequency of text messaging to promote medication adherence through focus groups; (2) identify the most patient-centered app that promotes adherence, through a content analysis of all commercially available apps for medication adherence and focus groups centered on usability; and (3) compare adherence to antiplatelet medications in Veterans after ACS/PCI via a randomized clinical trial (RCT).MethodsWe will utilize a mixed-methods design that uses focus groups to achieve the first and second aims (N=32). Patients will be followed for 12 months after being randomly assigned to one of three arms: (1) customized text messaging, (2) mobile app, or (3) website-control groups (N=225). Medication adherence will be measured with electronic monitoring devices, pharmacy records, and self-reports.ResultsEnrollment for the focus groups is currently in progress. We expect to enroll patients for the RCT in the beginning of 2018.ConclusionsDetermining the efficacy of mobile technology using a Veteran-designed protocol to promote medication adherence will have a significant impact on Veteran health and public health, particularly for individuals with chronic diseases that require strict medication adherence.Trial registrationClinicalTrials.gov NCT03022669.